Malignant gliomas are currently identified and followed by MRI. Neuro-imaging is expensive, frequently unavailable and may be insensitive to early changes in tumor size or degeneration. Identification of a serum marker that correlates with glioma grade and burden of disease would be of enormous assistance in clinical glioma management. Through a microarray analysis of a series of glioblastomas (GBM) we have identified a credible candidate protein, YKL-40, that may serve as a serum marker for patients with GBM. We are proposing a prospective clinical trial of patients with a range of glioma types and grade. Serum samples will be obtained throughout the course of their disease and linked to standard imaging studies to ascertain disease status. These sera will be used to test for YKL-40 levels and they will serve as a serum bank in which to test other potential markers as they are identified. We propose to search for other potential markers using gene expression microarray analysis and proteinomic technology. In addition, the signaling characteristics of tumor tissue taken from patients who are participating in the serum bank will be characterized and correlated to a given serum marker. For example, YKL-40 appears to correlate with tumor levels of activated Akt. If this is confirmed, YKL-40 may be useful not only as a serum marker but also as a surrogate for specific signal transduction abnormalities in the tumor itself. This has the potential to facilitate the design of specific therapy for a given patient's tumor. Finally, using proteinomic technology we plan to search for tumor markers in transgenic mice bearing brain tumors of known genetic characteristics. Ultimately we will seek to identify whether serum markers found in the mouse are also useful in humans with gliomas of similar histology.